Polymorphisms in the ABCC2 (cMOAT/MRP2) Gene Found in 72 Established Cell Lines Derived from Japanese Individuals: An Association between Single Nucleotide Polymorphisms in the 5′-Untranslated Region and Exon 28: Table 1

Abstract

We found nucleotide variability in the 5'-upstream region and exonic sequences of a gene-encoding canalicular multispecific organic anion transporter/multidrug resistance-associated protein 2 (cMOAT/MRP2) by polymerase chain reaction-based sequencing using genomic DNA from 72 established cell lines derived from 72 Japanese individuals. Four single nucleotide polymorphisms (SNPs) were found in the 5'-untranslational region and 21 in the exonic regions. Of them, 14 were nonsynonymous SNPs. One deletion of seven consecutive adenines resulting in a frameshift variant was also found. Four SNPs, c-24t, g1249a (V417I), c2366t (S789F), and c3972t (I1324I), were the same as those recently reported. A strong association was found between c-24t (5'-untranslated region) and c3972t (exon 28), with the promoter activity of the former worth being compared.

Homozygous mutation Arg768Trp in the ABC-transporter encoding gene MRP2/cMOAT/ABCC2 causes Dubin-Johnson syndrome in a Caucasian patient

“…Ito et al (2001) examined a panel of healthy Japanese specimens to detect mutations in the ABCC2 gene and found the mutation C2302T to be heterozygous in one of 48 specimens. In accordance with our results, Itoda et al (2002) could not detect the alteration C2302T in any of 72 cell lines derived from various tissues of healthy Japanese individuals for the purpose of detecting polymorphisms in the ABCC2 gene. It was reported that the amino acid exchange Arg 768 Trp causes a deficient maturation of the ABCC2 protein leading to a diminished glycosylation, impaired sorting to the apical membrane, and degradation via the proteasome pathway (Hashimoto et al 2002).…”

“…The DJScausing base substitution C2302T was not detected in any of the control specimens. In order to demonstrate that the used control subjects and cell lines are representative for the population, one of the most common polymorphisms of the ABCC2 encoding gene (Ito et al 2001;Mor-Cohen et al 2001;Itoda et al 2002), SNP C-24T, was analyzed. In four of 20 control individuals the SNP C-24T was detected, whereas the DJS patient did not show this polymorphism.…”

“…So far, several mutations and polymorphisms of the human ABCC2 gene have been reported (Wada et al 1998;Toh et al 1999;Ito et al 2001;Mor-Cohen et al 2001;Itoda et al 2002;Saito et al 2002). In this study, we report a mutation of the ABCC2 gene in a patient with DJS, which was also described to be a single nucleotide polymorphism (SNP) in healthy specimens by other authors (Ito et al 2001;Saito et al 2002).…”

Influence of polymorphisms of ABCB1 and ABCC2 on mRNA and protein expression in normal and cancerous kidney cortex

“…À24C4T and 3972C4T were in strong linkage disequilibrium (100% in patients and 92.5% in controls) as described before for a Japanese sample. 44 Interestingly, carriers homozygous for À24T exhibited 1.4 times lower median mRNA/ 18S rRNA ratios in non-cancerous cortex tissue than À24CC carriers (P ¼ 0.03). Moreover, subjects, homozygous for the haplotype À24T/3972T, exhibited a tendency of decreased ABCC2 mRNA expression than homozygote À24C/3972C carriers (P ¼ 0.053).…”

Pharmacogenetic determinants of variability in lipid-lowering response to pravastatin therapy

“…With regard to liver concentration of pravastatin, genetic polymorphisms of MRP2 might affect response to pravastatin. However, MRP2 variants have been observed at low frequency in Japanese (Itoda et al 2002), and functional significance of these variants is not established. Therefore, association of MRP2 genotypes should be analyzed by further studies.…”